[Hepatoblastoma and hemihypertrophy].
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Biomedical subjects
Publications and source records attributed to Z Spirer.
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The immunoglobulin heavy-chain-associated tetrapeptide, tuftsin (Thr-Lys-Pro-Arg), known for its phagocytosis-stimulating activity, was found to augment the antigen-specific, macrophage-dependent education of T lymphocytes. The investigation of stereospecific characteristics of the tetrapeptide, by use of structural analogs with different modifications, revealed strict structural requirements for eliciting the immunogenic activity of macrophages. It was found that the most important moiety for its activity is the dipeptide Pro-Arg. This finding is of interest in view of the appearance of this particular dipeptide in other bioregulatory peptides, including many of the peptide hormones. The significance of the appearance of a common structure in such molecules, which may act through specific receptors on different target cells, is discussed.
The cyclization, under alkaline conditions, of N-benzyloxycarbonyl-L-threonine and of N-benzyloxycarbonyl-L-serine to produce 5-methyl-2-oxo-oxazolidine-4-carboxylic acid (O = C Thr1 and 2-oxo-oxazolidine-4-carboxylic acid (O = C Ser), respectively, was investigated and found to be efficient and racemization-free. Similar was the cyclization which accompanied the basic hydrolysis of N-benzyl-oxycarbonyl-L-threonyl-L-phenylalanine methyl ester and of N-benzyloxy-carbonyl-L-seryl-DL-valine ethyl ester, and which resulted in the formation of L - O = C Thr-L-Phe and L - O = C Ser-DL-Val, respectively. The reaction was applied to the synthesis of [O = C Thr1] tuftsin, an active analog of the phagocytosis stimulating peptide tuftsin. A new synthetic route to tuftsin is also described.
In a retrospective analysis of 78 patients with liver cirrhosis, we found low serum levels of calcium and phosphorus. The low calcium levels showed a better correlation with high activity of aspartate aminotransferase than with low levels of albumin. In addition, there was a relationship between low calcium and low phosphorus levels. Therefore, factors other than, and in addition to, hypoalbuminemia seem to be responsible for the low calcium and phosphorus levels in cirrhosis patients. Although low levels of serum 25-hydroxyvitamin D were found in 23 of our patients, there was no indication that hypovitaminosis D was causative factor in the hypocalcemia and hypophosphatemia.
Serum tuftsin concentrations were measured, using a radioimmunoassay developed in Israel, in normal subjects and in patients who had undergone splenectomy. Concentrations in those who had undergone traumatic and elective splenectomy were much lower. The tuftsin concentration in 38 patients with Hodgkin's disease who had undergone splenectomy during staging laparotomy was not significantly different from the mean concentration in other patients who had had elective splenectomy. In four patients who underwent splenectomy for non-malignant haematological disorders measurements made before and after operation showed that tuftsin concentrations fell significantly in the days after operation. The increased susceptibility to overwhelming infections of patients with Hodgkin's disease and others who have undergone splenectomy may be related to the low tuftsin concentrations. As pre-splenectomy tuftsin concentrations in patients with Hodgkin's disease were normal, the practice of performing staging laparotomy and splenectomy in patients with Hodgkin's disease should perhaps be reconsidered.
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The mobilization of WBC from the bone marrow, as judged from hydrocortisone-induced leucocytosis, is markedly impaired in dialyzed and nondialyzed uremic patients. The release of WBC from the marginal pool by epinephrine was found to be normal.
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The phagocytosis-stimulating tetrapeptide tuftsin, L-threonyl-L-lysyl-L-prolyl-L-arginine, was synthesized by both conventional and polymeric-reagent approaches. Using a combination of the two methods several analogs were prepared, including: [Ala1]tuftsin, [Lys1]tuftsin, [Ser1]tuftsin, [Val1]tuftsin, acetyl-tuftsin, p-aminophenylacetyl-tuftsin and tyrosyl-tuftsin. [Des-Thr1]tuftsin and [omega-NO2(4)]tuftsin were synthesized using a conventional procedure. The effects of synthetic peptides on the phagocytosis of heat-killed yeasts and on the reduction of the dye nitroblue tetrazolium by normal human polymorphonuclear leukocytes were investigated. Tuftsin and to a lesser extent [Lys1]tuftsin and [Ser1]tuftsin were found to stimulate phagocytosis, whereas the other analogs synthesized as well as [Ser1]tuftsin exhibited inhibitory effects to tuftsin's action. Tuftsin alone has stimulated nitroblue tetrazolium reduction; [Des-Thr1]tuftsin and [Ala1]tuftsin repressed this stimulation, while the other peptides showed no effect.
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PPD stimulated lymphocyte reactivity was tested in 119 children aged 11 to 12 years. The lymphocyte responses was evaluated by measuring the extent of tritiated thymidine incorporation by cultured cells. In a group of sixty-four tuberculin negative children who had been BCG vaccinated in the neonatal period, lymphocyte response was significantly greater than in a group of non-vaccinated tuberculin negative children matched for sex. The highest reactivity appeared in another group of children vaccinated in infancy and tuberculin positive. Lymphocytes from BCG vaccinated children retain some sensitivity to tuberculin even years after the BCG vaccination and even at the time when the skin reactivity disappeared.
Two boys suffering from the hemolytic-uremic syndrome (HUS) are presented. One of them developed four episodes of the disease beginning at infancy, the other one had at least two episodes which were associated with mild portal fibrosis of the liver. Between the attacks of the disease, the children were completely healthy, and no renal or hematological abnormalities were detected. Both patients are now physically and mentally well developed healthy young men. The relatioship between HUS and thrombotic thrombocytopenic purpura is briefly discussed.
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